View source for 7ces


==Crystal structure of L-cycloserine-bound form of cysteine desulfurase SufS H121A from Bacillus subtilis==
<StructureSection load='7ces' size='340' side='right'caption='[[7ces]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ces]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CES FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7TS:(5-HYDROXY-6-METHYL-4-{[(3-OXO-2,3-DIHYDRO-1,2-OXAZOL-4-YL)AMINO]METHYL}PYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>7TS</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ces FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ces OCA], [https://pdbe.org/7ces PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ces RCSB], [https://www.ebi.ac.uk/pdbsum/7ces PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ces ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SUFS_BACSU SUFS_BACSU] Enzyme able to deliver sulfur to partners involved in Fe-S cluster assembly. Catalyzes the removal of elemental sulfur atoms from L-cysteine to produce L-alanine. Activity is stimulated 40-to 100-fold by SufU, which acts as a second substrate for this enzyme following release of Ala, and generating SufU.S. A mixture of SufS, SufU, Fra and L-cysteine is able to reconstitute Fe-S clusters on apo-aconitase (citB), reconstituting aconitase activity.<ref>PMID:20097860</ref> <ref>PMID:20822158</ref> <ref>PMID:21744456</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cysteine desulfurase SufS is a pyridoxal-5'-phosphate-dependent enzyme and is essential for the SUF system, which participates in iron-sulfur cluster biosynthesis. Inhibition of SufS in the SUF system by D-cycloserine (DCS) in Plasmodium falciparum apicoplast has recently been reported, indicating that SufS could be a target for malaria therapeutics. However, the mechanistic details underlying the inhibition of SufS by DCS have not yet been clarified. Moreover, inhibition of SufS by the other enantiomer, L-cycloserine (LCS), has not been investigated. Herein, we investigated the structure-based inhibition mechanisms of SufS by DCS and LCS using Bacillus subtilis SufS, whose catalytic mechanism has been well characterized in comparison to that of the P. falciparum SufS. Surprisingly, DCS- and LCS-mediated inhibitions of SufS occur via distinct mechanisms resulting in pyridoxamine-5'-phosphate (PMP) in DCS-mediated inhibition and PMP-3-hydroxyisoxazole adduct (PMP-isoxazole) in LCS-mediated inhibition. Biochemical and structural evaluation of SufS variants identified conserved His and Arg residues at the active site as the key determinants of the distinct inhibition mechanisms. The importance of structural elements involved in DCS and LCS-mediated inhibitions of SufS provides valuable insights for the structure-based design of new drugs targeting SufS. DATABASE: Structural data are available in PDB database under the accession numbers 6KFY, 7CEO, 7CEP, 7CEQ, 7CER, 7CES, 7CET, 7CEU, 7E6A, 7E6B, 7E6C, 7E6D, 7E6E, and 7E6F.

Cycloserine enantiomers inhibit PLP-dependent cysteine desulfurase SufS via distinct mechanisms.,Nakamura R, Ogawa S, Takahashi Y, Fujishiro T FEBS J. 2022 Apr 8. doi: 10.1111/febs.16455. PMID:35395703<ref>PMID:35395703</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ces" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cysteine desulfurase 3D structures|Cysteine desulfurase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Bacillus subtilis subsp. subtilis str. 168]]
[[Category: Large Structures]]
[[Category: Fujishiro T]]
[[Category: Nakamura R]]
[[Category: Takahashi Y]]